Evidence map›Paper›PMID 40175378›Full record

ArticleNPJ Regenerative medicine2025

Preclinical efficacy and safety of AAVrh10-based plakophilin-2 gene therapy (LX2020) as a treatment for arrhythmogenic cardiomyopathy.

Jing Zhang, Erika Joana Gutierrez-Lara, Aryanne Do, Lena Nguyen, Anju Nair, Nithya Selvan, Tim Fenn, Eric Adler, Richie Khanna, Farah Sheikh

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ Regenerative medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Jing ZhangDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Erika Joana Gutierrez-LaraDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Aryanne DoDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Lena NguyenDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Anju NairLEXEO Therapeutics Inc, New York, NY, USA.
Nithya SelvanLEXEO Therapeutics Inc, New York, NY, USA.
Tim FennLEXEO Therapeutics Inc, New York, NY, USA.
Eric AdlerLEXEO Therapeutics Inc, New York, NY, USA.
Richie KhannaLEXEO Therapeutics Inc, New York, NY, USA. rkhanna@lexeotx.com.
Farah SheikhDepartment of Medicine, University of California San Diego, La Jolla, CA, USA. fasheikh@health.ucsd.edu.

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Uncovering Molecular Targets for Arrhythmogenic Cardiomyopathy TherapeuticsR01HL162369 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHEIKH, FARAH · 2022 to 2025
$2.0M
Uncovering New Functions of CSN6 in Cardiac Desmosomal Biology and DiseaseR01HL142251 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHEIKH, FARAH · 2018 to 2021
$1.6M
Understanding Early Drivers and Therapeutic Targets for Severe Forms of Arrhythmogenic CardiomyopathyR01HL181001 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Farah Sheikh · 2025 to 2026
$1.4M
NHLBI NIH HHS R01 HL142251NHLBI NIH HHS R01 HL162369NHLBI NIH HHS R01 HL181001NIH HHS HL142251NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Plakophilin-2 (PKP2) mutations cause fatal genetic heart disease and arrhythmogenic cardiomyopathy (ACM) with primary effects on the right ventricle (RV). Adeno-associated virus (AAV)-PKP2 gene therapy shows promise as a therapeutic strategy but lacks long-term data and guidelines on minimal effective doses in animal studies for treating RV deficits, arrhythmia burden, and improving survival when administered during disease settings, which are most relevant to clinical trials. Using AAVrh10, known for its preferential cardiac gene expression at lower doses, we show minimal doses required for efficacy for AAVrh10.PKP2 (LX2020) to rescue cardiac (molecular and especially RV) deficits, arrhythmia burden and survival in PKP2 ACM mice, suggesting its potential to reverse late-stage pathology. Safety assessments in non-human primates revealed no adverse events. These data support LX2020 as a viable treatment for PKP2 ACM patients.

Identifiers

PMID40175378
PMCPMC11965304

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.